Allen Discovery Center at Tufts University, Department of Biology, Tufts University, Medford, Massachusetts.
Allen Discovery Center at Tufts University, Department of Biology, Tufts University, Medford, Massachusetts.
Biophys J. 2019 Mar 5;116(5):948-961. doi: 10.1016/j.bpj.2019.01.029. Epub 2019 Feb 1.
Axial patterning during planarian regeneration relies on a transcriptional circuit that confers distinct positional information on the two ends of an amputated fragment. The earliest known elements of this system begin demarcating differences between anterior and posterior wounds by 6 h postamputation. However, it is still unknown what upstream events break the axial symmetry, allowing a mutual repressor system to establish invariant, distinct biochemical states at the anterior and posterior ends. Here, we show that bioelectric signaling at 3 h is crucial for the formation of proper anterior-posterior polarity in planaria. Briefly manipulating the endogenous bioelectric state by depolarizing the injured tissue during the first 3 h of regeneration alters gene expression by 6 h postamputation and leads to a double-headed phenotype upon regeneration despite confirmed washout of ionophores from tissue. These data reveal a primary functional role for resting membrane potential taking place within the first 3 h after injury and kick-starting the downstream pattern of events that elaborate anatomy over the following 10 days. We propose a simple model of molecular-genetic mechanisms to explain how physiological events taking place immediately after injury regulate the spatial distribution of downstream gene expression and anatomy of regenerating planaria.
涡虫再生过程中的轴向模式依赖于一个转录回路，该回路赋予被切断的片段两端不同的位置信息。该系统最早被认识的部分在截肢后 6 小时开始区分前后伤口之间的差异。然而，目前尚不清楚是什么上游事件打破了轴向对称，使得相互抑制系统在前后两端建立不变的、独特的生化状态。在这里，我们表明，在再生的前 3 小时内，生物电信号对于涡虫的正确前后极性的形成至关重要。在再生的前 3 小时内短暂地通过去极化损伤组织来操纵内源性生物电状态，会在截肢后 6 小时改变基因表达，并导致再生后出现双头表型，尽管已经证实从组织中冲洗掉了离液剂。这些数据揭示了在损伤后 3 小时内发生的静息膜电位的主要功能作用，并启动了随后 10 天内详细阐述解剖结构的下游事件模式。我们提出了一个简单的分子遗传机制模型，以解释损伤后立即发生的生理事件如何调节下游基因表达和再生涡虫解剖结构的空间分布。
